FUNCtion ALS: Aiming to Restore UNC13A Function in People Living With ALS

A Randomized, Double-Blind, Placebo-Controlled, Phase 1 / 2 Trial Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Exploratory Efficacy of TRCN-1023 Administered by Intrathecal Injections to Adult People Living With Amyotrophic Lateral Sclerosis

The FUNCtion Amyotrophic Lateral Sclerosis (ALS) trial is a randomized, double-blind, placebo-controlled Phase 1/2 trial to evaluate the safety and tolerability of TRCN-1023 in adults living with ALS. TRCN-1023 is an investigational medicine given as a single injection into the fluid surrounding the spine (intrathecal injection). The trial will also assess how the body processes the drug and whether it shows early signs of benefit over 24 weeks.

TRCN-1023 is an investigational medicine designed to restore the function of a protein called UNC13A, which becomes disrupted in most people with Amyotrophic Lateral Sclerosis (ALS) due to a breakdown in how nerve cells process genetic information. This trial is designed to evaluate the safety and tolerability of TRCN-1023 given as a single injection into the fluid surrounding the spine, and to identify the best dose to carry forward into future studies. TRCN-1023 stays in the brain and spinal cord long enough that it may only need to be administered once every 24 weeks. The trial will also assess how the body processes the drug, whether it engages its intended target, and its effects on disease progression, physical function, and quality of life.

Key Inclusion Criteria:

• Adults aged 18 to 75 years
• Diagnosis of ALS (clinically definite, clinically probable, or clinically probable laboratory supported)
• ALS symptoms began within the past 24 months
• Able to perform breathing tests: slow vital capacity (SVC) with consistent results, with breathing capacity of at least 60% of the expected value
• Able and willing to meet all study requirements, including travel to the study site, brain magnetic resonance imaging (MRI) scans, lumbar punctures, and blood draws
• Able and willing to use wearable sensors and complete speech assessments at home
• On a stable dose of approved ALS medication for at least 4 weeks prior to screening
• Capable of providing informed consent

Key Exclusion Criteria:

• Carries a confirmed SOD1 or FUS gene mutation
• Has a tracheostomy or requires continuous assisted ventilation more than 22 hours per day during the preceding 3 months before the first Screening Visit
• Has a contraindication to brain MRI (e.g., pacemaker, metal implants)
• Has a contraindication to lumbar puncture or spinal injection (e.g., blood clotting disorders, certain blood thinners, signs of increased pressure in the brain)
• Has significant abnormal liver, kidney, or blood test results
• Is currently enrolled in another clinical trial or has received an investigational treatment within the past 4 weeks
• Has previously received gene therapy, stem cell therapy, or another Antisense oligonucleotide (ASO) treatment
• Has a clinically significant condition other than ALS that could interfere with study participation